In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 157-157
Abstract:
157 Background: In this large phase III trial, median progression-free survival (PFS) improved by 5.1 mo with E+O compared to P+O in patients (pts) with NET associated with carcinoid syndrome. Randomization imbalances including WHO performance status (PS), and primary site favoring P+O confounded primary analysis. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers in NET. Analyses were performed to identify prognostic factors and adjust for randomization imbalances. Methods: Pts were randomized to E+O (n=216) or P+O (n=213). Potential prognostic factors including baseline CgA (≤2×ULN vs 〉 2×ULN), baseline 5-HIAA (≤median vs 〉 median), age ( 〈 65 vs ≥65), gender, race, WHO PS (0 vs 1, 2), primary site (lung vs other), prior somatostatin analog use (yes vs no), duration from diagnosis ( 〈 6 mo, 6-24 mo, 2-5 yr, 〉 5 yr), and organs involved (liver, bone) were assessed in univariate analysis using the log rank test and a stepwise regression using Cox proportional hazards model. Results: Randomization resulted in significant imbalance in baseline CgA (median [ng/mL], 251 E+O vs 137 P+O). Median PFS (mo) was significantly longer for pts with nonelevated CgA (27 vs 11; P 〈 .001) and nonelevated 5-HIAA (17 vs 11; P 〈 .001). Analyses also indicated age (14 vs 12; P=.01), WHO PS (17 vs 11; P=.004), liver involvement (14 vs not reached; P=.02), bone metastases (8 vs 15; P 〈 .001), and lung as primary site (11 vs 14; P=.06) as potentially prognostic. Multivariate analysis indicated that significant prognostic factors for PFS included baseline CgA (HR, 0.47; CI, 0.34-0.65; P 〈 .001), WHO PS (HR, 0.69; CI, 0.52-0.90; P=.006), bone involvement (HR, 1.52; CI, 1.06-2.18; P=.02), and lung as primary site (HR, 1.55; CI, 1.01-2.36; P=.04). Adjusted for covariates, a 38% reduction in risk of progression was observed for E+O (HR, 0.62; 95% CI, 0.51-0.87; P=.003). Conclusions: In the phase III RADIANT-2 trial, baseline CgA levels, WHO PS, lung as primary site, and bone involvement were important prognostic factors. Exploratory analysis adjusted for these prognostic factors indicated significant benefit for everolimus therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.4_suppl.157
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
detail.hit.zdb_id:
604914-X
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